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. 2023 Nov 5;6(11):e1686.
doi: 10.1002/hsr2.1686. eCollection 2023 Nov.

Exploration of the common pathogenic link between COVID-19 and diabetic foot ulcers: An in silico approach

Xueyao Cai  1 , Ruijin Yang  1 , Wenjun Shi  2 , Yuchen Cai  2 , Zhengzheng Ma  1
Affiliations

Exploration of the common pathogenic link between COVID-19 and diabetic foot ulcers: An in silico approach

Xueyao Cai et al. Health Sci Rep. .

Abstract

Background and aims: The Coronavirus Disease-19 (COVID-19) is posing an ongoing threat to human health. Patients of diabetic foot ulcer (DFU) are susceptible to COVID-19-induced adverse outcomes. Nevertheless, investigations into their mutual molecular mechanisms have been limited to date. In the present work, we tried to uncover the shared pathogenesis and regulatory gene targets of COVID-19 and DFU.

Methods: In this study, we chose GSE161281 as the COVID-19 data set, which contained severe acute respiratory syndrome coronavirus 2 infected human induced embryonic stem cell-derived peripheral neurons (n = 2) with uninfected controls (n = 2). The GSE134431 designated as the DFU data set, comprising full-thickness DFU (n = 13) and diabetic foot skin (n = 8) samples from diabetic patients. The differential expressed genes (DEGs) were identified from GSE161281 and GSE134431, and the common DEGs between COVID-19 and DFU were extracted. Multifactor regulatory network and co-expression network of the common DEGs were analyzed, along with candidate drug prediction.

Results: Altogether, six common DEGs (dickkopf-related protein 1 [DKK1], serine proteinase inhibitor A3 [SERPINA3], ras homolog family member D [RHOD], myelin protein zero like 3 [MPZL3], Claudin-11 [CLDN11], and epidermal growth factor receptor pathway substrate 8-like 1 [EPS8L1]) were found between COVID-19 and DFU. Functional analyses indicated that pathways of apoptotic and Wnt signaling may contribute to progression of COVID-19. Gene co-expression network implied the shared pathways of immune regulation and cytokine response participated collectively in the development of DFU and COVID-19. A multifactor regulatory network was constructed integrating the corresponding microRNAs (miRNAs) and transcription factors. Additionally, we proposed potential drug objects for the combined therapy.

Conclusion: Our study revealed the shared molecular mechanisms underlying COVID-19 and DFU. The identified pivotal targets and common pathways can provide new perspectives for further research and assist the development of management strategies in patients of DFU complicated with COVID-19.

Keywords: COVID‐19; diabetic foot ulcer; differentially expressed genes; regulatory network; therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Workflow diagram of the present study.
Figure 2
Figure 2
Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the differentially expressed genes (DEGs) in COVID‐19. GO analysis including (A) biological process (BP), (B) cellular component (CC), and (C) molecular function (MF). (D) KEGG analysis.
Figure 3
Figure 3
Venn diagram identified an overlap of six common differentially expressed genes (DEGs) between COVID‐19 and diabetic foot ulcer (DFU).
Figure 4
Figure 4
Common differentially expressed genes (DEGs) and their co‐expression genes analyzed via GeneMANIA.
Figure 5
Figure 5
Gene regulatory network integrating the hub genes (mRNAs), microRNAs (miRNAs), and transcription factors (TFs). The green rectangles represent for hub genes (mRNAs), blue triangles for miRNAs, and red diamonds for TFs.
Figure 6
Figure 6
Analysis of top 10 candidate drugs associated with hub genes between COVID‐19 and diabetic foot ulcer (DFU).
See this image and copyright information in PMC

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